The purpose of this study was to characterize the effect of chlordecone or estrogen on the rat pituitary level of (Met5)-enkephalin (ME) and to examine the possibility that the modulation of pituitary ME by chlordecone may be mediated through its estrogenic-like activity. The anterior pituitary enkephalin system is regulated by circulating sex hormones. Androgen increases, whereas estrogen decreases, the level of pituitary enkephalin. Chlordecone exerts robust effects on the hypothalamo-pituitary axis such as pituitary enkephalin system and the estrogenic activity of this insecticide may mediate some of its effects on the neuroendocrine function. Both estrogen and chlordecone decrease the level of enkephalin in the pituitary but increase the level of this peptide in the striatum. Since estrogen exerts antidopaminergic activity both in the striatum and in the pituitary plus the fact that the enkephalin systems in these two regions are regulated by dopamine, it is possible that the effect of estrogen and chlordecone on the pituitary and striatal enkephalin systems is mediated through the dopaminergic system.